Method for the preparation of 2-hydroxyarylaldoximes

ABSTRACT

A method for the preparation of a 2-hydroxyarylaldoxime which comprises reacting hydroxylamine with a 2-hydroxyarylaldehyde, said reaction being performed in the presence of a compound of a metal of Group II, Group III, Group IVA or Group VIA of the Periodic Table and/or under such conditions that the 2-hydroxyarylaldehyde is at least partially in the form of a salt and/or complex of a metal of Group II, Group III, Group IVA or Group VIA of the Periodic Table.

This invention relates to a chemical process and more particularly to amethod for the preparation of 2-hydroxyarylaldoximes.

The use of 2-hydroxyarylaldoximes (salicylaldoximes) as extractants inthe hydrometallurgical recovery of metals from metal ores is well known.The process is described, for example, in GB-A-1421766 and has beenpractised commercially for a number of years.

The 2-hydroxyarylaldoximes may be obtained in conventional manner byreacting the corresponding 2-hydroxyarylaldehyde with hydroxylamine. Inpractice, the hydroxylamine is usually employed in the form of a salt,for example hydroxylammonium sulphate or chloride, and the reaction isperformed in the presence of an acid-binding agent such as sodiumcarbonate which reacts with the liberated acid forming sodium sulphateor chloride, which has to be disposed of, and carbon dioxide. Since thereaction is commonly carried out in a two-phase aqueous and organicsolvent medium, the evolution of carbon dioxide can cause loss oforganic solvent with economic and environmental consequences unlessappropriate and often expensive precautions are taken.

It has now been found that the problems associated with currentprocesses for the preparation of 2-hydroxyarylaldoximes may be obviatedor minimised if the 2-hydroxyarylaldehyde is used, at least partially,in the form of a salt and/or complex of certain metals as hereinafterdescribed or in the presence of a compound of said metals. In somecases, a much faster reaction occurs than is the case in theconventional process described above and, furthermore, integration ofthe oximation reaction with a formylation reaction for preparing thealdehyde allows additional operational savings.

Accordingly, the present invention provides a method for the preparationof a 2-hydroxyarylaldoxime which comprises reacting hydroxylamine with a2-hydroxyarylaldehyde, said reaction being performed in the presence ofa compound of a metal of Group II, Group III, Group IVA or Group VIA ofthe Periodic Table and/or under such conditions that the2-hydroxyarylaldehyde is at least partially in the form of a salt and/orcomplex of a metal of Group II, Group III, Group IVA or Group VIA of thePeriodic Table.

As examples of 2-hydroxyarylaldehydes which may be used in the method ofthe invention, there may be mentioned compounds of the formula: ##STR1##wherein each of R¹, R², R³ and R⁴, independently, represents a hydrogenor halogen atom or an alkyl, cycloalkyl, aralkyl, aryl, alkaryl, alkoxy,aryloxy, acyl or hydroxy group. Each of the various hydrocarbyl,hydrocarbyloxy and acyl groups which may be represented by R¹, R², R³and R⁴, suitably contains up to 36 carbon atoms, for example from 5 to22 carbon atoms.

Particular mention may be made of 2-hydroxyarylaldehydes of the formula:##STR2## wherein R⁵ represents hydrogen or a C₁₋₂₂ -alkyl radical, saidcompounds being used in the preparation of 2-hydroxyarylaldoximes of theformula: ##STR3## Preferably, R⁵ is a C₇₋₁₂ -alkyl radical, especiallyin the 4-position relative to the hydroxyl group.

Because of the presence of the compound of a metal of Group II, GroupIII, Group IVA or Group VIA of the Periodic Table, it is believed thatthe 2-hydroxyarylaldehyde will be present in the reaction mixture, atleast partially, in the form of a salt, that is to say an aryloxide,and/or a complex of said metal. As examples of particularly suitablemetals, there may be mentioned magnesium (Group IIA), aluminium (GroupIIIB), titanium and zirconium (Group IVA), and chromium (Group VIA). Ametal salt and/or complex of the hydroxyarylaldehyde may be pre-formedor may be generated in the reaction mixture, perhaps only transientlyand possibly in equilibrium with one or more other derivatives of themetal.

Reaction conditions suitable for the preparation of2-hydroxyarylaldehydes in the form of magnesium salts have beendescribed in our EP-A-0529870. Conditions under which2-hydroxyarylaldehydes may be prepared in the presence of compounds ofaluminium, titanium, zirconium and chromium have been described inEP-A-0077279, EP-A-0106653 and U.S. Pat. No. 4,231,967 and theseconditions may be expected to lead to the formation of the2-hydroxyarylaldehyde, at least partially, in the form of salts and/orcomplexes of said metals.

In performing the method of the invention, the hydroxylamine mayadvantageously be used in the form of a salt, for example an aqueoussolution of a salt. Suitable salts include hydroxylammonium bromide,phosphate, nitrate and acetate but especially the sulphate.

When the hydroxylamine is employed in the form of a salt and thehydroxyarylaldehyde is used in partial salt form, the metal compoundbeing present in less than a chemically equivalent amount relative tothe hydroxyarylaldehyde, for example a catalytic amount of a titaniumcompound, it will usually be necessary to perform the reaction in thepresence of a base. Suitable bases include alkali metal hydroxides,carbonates, acetates and the like and nitrogenous bases. When the metal,for example magnesium, is used in at least a chemically equivalentamount relative to the hydroxyarylaldehyde, the addition of a furtherbase as acid-binding agent is not usually necessary.

The reaction upon which the method of the invention is based may beconveniently performed in a suitable solvent medium at temperatures offrom 30° to 150° C. although somewhat lower or higher temperatures maybe employed if desired. Suitable solvent media include organic solventssuch as alcohols in which both the hydroxyarylaldehyde and thehydroxylamine are soluble to a significant extent. It is preferred,however, to employ the hydroxylamine or salt thereof in the form of anaqueous solution. The hydroxyaldehyde, being at least partially in theform of a salt and/or complex of the metal, may, depending upon itsstructure and also upon the degree of ionisation, be used as such or inthe form of a solution or dispersion in water or in a water-miscible orwater-immiscible organic solvent. Preferred solvent systems includemixtures of water and an aromatic hydrocarbon such as toluene or xylene.

The 2-hydroxyarylaldoxime reaction product may be recovered from thereaction mixture in which it is prepared in any conventional manner.

The method of the invention is of particular value for the preparationof 2-hydroxyarylaldoximes by reacting hydroxylamine or a salt thereofwith a magnesium salt (bis-aryloxide) of a 2-hydroxyarylaldehyde,especially a 2-hydroxyarylaldehyde of Formula 1 or Formula 2 above andespecially for the preparation of the metal extractant5-nonylsalicylaldoxime from the corresponding magnesiumbis-(2-formyl-4-nonylphenoxide).

The method of the invention is also valuable for the preparation of2-hydroxyarylaldoximes by reacting hydroxylamine or a salt thereof witha 2-hydroxyarylaldehyde, especially a 2-hydroxyarylaldehyde of Formula 1or Formula 2 above, in the presence of a titanium (IV) derivative.Suitable titanium (IV) derivatives include compounds of the formula:##STR4## wherein each of W, X, Y and Z, independently, represents ahalogen atom or an alkoxy, aryloxy, alkaryloxy, aralkoxy, acyloxy orcyclopentadienyl group or a residue of a β-diketone, a hydroxyquinolineor an optionally substituted 2-hydroxybenzaldehyde, or two of W, X, Yand Z together represent an oxygen atom, each of the remaining two,independently, representing a halogen atom or an alkoxy, aryloxy,aralkoxy, alkaryloxy or acyloxy group or a residue of a β-diketone, ahydroxyquinoline or an optionally substituted 2-hydroxybenzaldehyde.Generally, the alkyl or acyl part of a group W, X, Y or Z will containup to 22 carbon atoms and the aryl part will be phenyl.

Specific examples of titanium (IV) derivatives include titaniumtetraisopropoxide, titanium tetrabutoxide and titanium tetraphenoxide.

Methods for the preparation of 2-hydroxyarylaldehydes by theortho-formylation of optionally substituted phenols in the presence ofvarious metal derivatives have been described in the aforementionedreferences. In accordance with these methods, 2-hydroxyarylaldehydes arebelieved to be obtained at least partially in the form of metal saltsand/or complexes from with the aldehyde itself may be recovered byconventional techniques, for example by acidification and extraction. Itis a particularly advantageous feature of the present invention that the2-hydroxyarylaldehydes obtained in said formylation processes may beused directly as starting materials without needing to isolate them fromthe reaction mixtures containing the metal derivatives.

Accordingly, a further aspect of the present invention provides a methodfor the preparation of a 2-hydroxyarylaldoxime which comprises reactinghydroxylamine with a 2-hydroxyarylaldehyde which is the direct productof reacting a phenol having at least one free ortho position withformaldehyde or a formaldehyde-liberating compound under substantiallyanhydrous conditions in the presence of a compound of a metal of GroupII, Group III, Group IVA or Group VIA of the Periodic Table.

In a preferred embodiment of this aspect of the invention, hydroxylamineor a hydroxylamine salt is reacted with a magnesium 2-formylphenoxideobtained by reacting a magnesium bis-hydrocarbyloxide derived at leastin part from a hydroxyaromatic compound having at least one freeposition ortho to the hydroxyl group with formaldehyde or a formaldehydeliberating compound under substantially anhydrous conditions.

In an especially preferred embodiment of this aspect of the invention,hydroxylamine or a hydroxylamine salt is reacted with a magnesiumbis(2-formylphenoxide) obtained by reacting a magnesium bis-phenoxidederived from a phenol having at least one free ortho position withformaldehyde or a formaldehyde-liberating compound under substantiallyanhydrous conditions.

The substantially anhydrous conditions required by the formylationreaction for production of the magnesium bis(2-formylphenoxide) may beconveniently provided by the use of substantially anhydrous reactantstogether with conventional techniques, for example distillation, forremoval of adventitious moisture. It is usually advantageous to performthe reaction in the presence of a substantially anhydrous solventsystem. Suitable solvent systems typically comprise an inert non-polaror low polarity organic solvent and/or a polar organic solvent capableof acting as a ligand with respect to magnesium atoms.

Suitable inert non-polar or low polarity organic solvents will beliquids at the reaction temperature and will act as solvents for themagnesium bis-hydrocarbyloxide. Preferably, they will allow removal ofone or more of the volatile by-products by distillation. Examples ofsuitable inert solvents include aromatic hydrocarbons, for exampletoluene, xylene, mesitylene, cumene, cymene, tetralin and chlorinatedaromatic hydrocarbons, for example chlorobenzene and o-dichlorobenzene.Mixtures of inert solvents may be used.

Suitable polar solvents will be liquids at the reaction temperature andmay be regarded as co-solvents when used in conjunction with non-polaror low polarity solvents. As examples of suitable polar co-solvents,there may be mentioned polar aprotic solvents such asdimethylsulphoxide, sulpholane, dimethylacetamide, N-formylpiperidine,N-methylpyrrolidinone, tetramethylurea and, especially,dimethylformamide, tertiary bases such as triethylamine, tri-octylamine,tetramethylethylenediamine and pyridine, ethers such as diethyl ether,diphenyl ether, tetrahydrofuran, glyme, diglyme, triglyme,tris[2-(2-methoxyethoxy)ethyl]amine and crown ethers and other polarsolvents such as "Polymeg" 1000 and "Cellosolve" and the like.Particularly useful co-solvents include lower alkanols such as ethanoland, especially, methanol. Mixtures of co-solvents may be used. Theco-solvent may be incorporated into the reaction mixture as such or inthe form of a ligand already complexed with the magnesium atoms of thebis-aryloxide.

Some solvent materials may have the ability to function as both"solvent" and "co-solvent" in the method of the invention. Thus, forexample, a material such as tetrahydrofuran may be used as a solvent inconjunction with a higher polarity co-solvent or as a co-solvent inconjunction with a lower polarity solvent or it may be used as the solesolvent/co-solvent.

The formylation reaction used to prepare the magnesiumbis-(2-formylphenoxide) is suitably performed at a reflux temperaturewithin the range from about 60° to about 130° C., by-products of thereaction, for example methanol, methyl formate and methylal, preferablybeing removed from the reaction mixture as they are formed. The refluxtemperature, in any particular case, will depend upon the constitutionof the solvent system and upon the pressure being exerted on thereaction zone. Formylation may be satisfactorily performed atatmospheric or higher pressures but, in some cases, it is preferred tocarry out the formylation at reduced pressures, that is to say atpressures lower than normal atmospheric pressure, for example atpressures of from 50 to 700 mm Hg (absolute). In particular, it has beenfound that, in addition to facilitating removal of volatile reactionby-products, a significant improvement in the yield and/or purity ofaldehyde and an appreciable reduction in formation of by-products areobserved when the reaction is carried out at reduced pressure (andconsequently at a lower temperature) compared with carrying out the samereaction in the same solvent system at atmospheric pressure.

In some cases, it may be preferable to carry out the reaction at areflux temperature in the range from about 70° to about 80° C., forexample about 75° C., the reaction pressure being selected to maintaindistillation of reaction by-products. Pressures in the range from about50 to about 500 mm Hg (absolute) will generally provide the preferredreflux temperatures.

Magnesium bis-hydrocarbyloxides which may be used in the formylationreaction are compounds containing two hydrocarbyloxy residues permagnesium atom, at least one of said hydrocarbyloxy residues beingaryloxy, for example phenoxy or naphthyloxy, having at least one freeposition ortho to the oxygen atom. Especially suitable are magnesiumbis-phenoxides wherein the phenoxide residues may be unsubstituted ormay be substituted in any or all of the positions, other than both the2- and 6-positions, by substituents which do not interfere with thecourse of the reaction and which preferably are electron-donating orweakly electron-withdrawing.

Especially useful magnesium bis-phenoxides are derivatives of phenols ofthe fomula: ##STR5## wherein each of R¹, R², R³ and R⁴ have the meaningsgiven above.

Particular mention may be made of magnesium bis-phenoxides derived fromphenols of the formula: ##STR6## wherein R⁵ is as defined above.

The magnesium bis-phenoxides derived from phenols of Formula 5 orFormula 6 may be regarded as compositions containing structures ofFormula 7 or Formula 8 respectively as well as related but more complexstructures containing more than one magnesium atom per molecule.

In structures of Formula 7: ##STR7## each of R¹, R², R³ and R⁴ is asdefined above, L represents a ligand molecule derived from anothercomponent of the reaction mixture and n represents an integer from 1 to6.

In structures of Formula 8: ##STR8## R⁵, L and n are as defined above.

Components of the formylation reaction mixture which may provide theligand molecules L include the co-solvent, formaldehyde and the methanolby-product and mixtures thereof.

It is particularly convenient, however, to use a magnesium bis-aryloxidewhich, because of its method of preparation, already containsappropriate ligand molecules.

Thus, it is preferred to use a magnesium bis-hydrocarbyloxide which hasbeen prepared by the method described by Ramirez et al in Synthesis,1979, 71, that is to say by reacting a magnesium alkoxide of theformula:

    Mg(OR.sup.6).sub.2                                         ( 9)

wherein R⁶ represents an alkyl, for example a C₁₋₄ -alkyl, radical,especially methyl, with up to two moles of a phenol having at least oneunsubstituted position adjacent to the phenolic hydroxyl group, forexample a phenol of Formula 5 or Formula 6. Preferred ratios are from0.9 to 2, especially from 1.5 to 2, typically about 1.66, moles ofphenol per mole of magnesium alkoxide.

The magnesium bis-aryloxides, when used in the formylation reactioncontain two aryloxy residues per magnesium atom and are believed also tocontain one or more ligand molecules or groups, for example methanolmolecules, such that they correspond or are structurally analogous toformula 7. It is to be understood, however, that the present inventionis not based upon any theory as to the precise structure of themagnesium bis-phenoxides and is to be regarded as relating to the use ofsaid bis-phenoxides whether in the form of complexes of Formula 7 ornot.

Other magnesium bis-hydrocarbyloxides which may be used in the method ofthe invention include compounds containing one aryloxy and one otherhydrocarbyloxy, for example alkoxy, residue per magnesium atom. Suchbis-hydrocarbyloxides may be obtained, for example, by reacting one moleof a magnesium alkoxide of Formula 9 with approximately one mole of aphenol having at least one unsubstituted position adjacent to thephenolic hydroxyl group and may, if desired, be used alone or inadmixture with the aforementioned bis-aryloxides.

The formaldehyde used in the method of the invention may be in the formof free gaseous formaldehyde or a solution in an anhydrous solvent or aformaldehyde-liberating compound, that is to say a compound capable ofliberating formaldehyde under the conditions employed in the method ofthe invention. Suitable formaldehyde-liberating compounds includepolymeric forms of formaldehyde such as paraformaldehyde. It ispreferred to add the formaldehyde or formaldehyde-liberating compoundgradually (continuously or discontinuously) to the bis-aryloxide in thesolvent system.

The formaldehyde or formaldehyde-liberating compound is generallyemployed in the method of the invention in an amount of at least twomoles, expressed as formaldehyde (HCHO), per mole of phenol present inthe bis-hydrocarbyloxide. Preferred ratios are from 2 to 3, typicallyabout 2.75 moles of formaldehyde per mole of phenol in thebis-hydrocarbyloxide. The co-solvent is suitably used in an amount notexceeding 5 moles per mole of bis-hydrocarbyloxide, preferred amountsbeing in the range from 1 to 2 moles per mole of bis-hydrocarbyloxide.These amounts include any co-solvent already present as ligand in thebis-hydrocarbyloxide. Since methanol is a by-product of the reaction,conversion and yield may be maximised by removing this methanol and anyother volatile by-products by distillation during the course of thereaction so as to maintain the co-solvent/bis-phenoxide ratio at theoptimum level.

In a further valuable embodiment of the invention, hydroxylamine or asalt thereof may be reacted directly with the aluminium, titanium,zirconium or chromium derivatives of 2-hydroxyarylaldehydes obtained inthe formylation reactions described in EP-A-0077279, EP-A-0106653 andU.S. Pat. No. 4,231,967 without the need to isolate the hydroxyaldehydesthemselves from the reaction mixtures in which they are formed.

The invention is illustrated but not limited by the following Examples.

EXAMPLE 1

Methanol (224 g) and toluene (98 g) were charged to a 2 liter glassreaction vessel followed by magnesium raspings (2.92 g). An activatorsolution (10 g) was added to activate the magnesium and the mixture washeated to reflux temperature (65° C.) to achieve magnesium dissolutionwith evolution of hydrogen gas. The mixture was maintained at refluxtemperature for 0.5 hour and then further magnesium was added in fourportions (4×2.92 g) over a total period of 1.5 hours, each portion beingadded once hydrogen evolution from the previous portion had subsided.The mixture was then heated under reflux for a further hour to ensurecomplete magnesium dissolution, 4-nonylphenol (224 g) was added and themixture heated under reflux for 1 hour to achieve nonylphenol magnesiumsalt formation. The activator solution was taken from a composition(1116 g) containing nonylphenol magnesium salt (461 g), magnesiummethoxide (17.3 g), toluene (194 g) and methanol (443.7 g).

Toluene (175 g) was added and methanol-toluene azeotrope (292 g) wasremoved by distillation until the reaction mixture temperature reached90°-95° C. An agitated slurry of paraformaldehyde (85 g) in toluene (120g) was added to the resulting toluene solution of the nonylphenolmagnesium salt at 90°-95° over 3 hours with removal of toluene andvolatile by-product distillates (100 g). On completion ofparaformaldehyde addition, the reaction mixture was heated to 95°-100°C. for 1 hour to ensure completion of reaction and the mixture was thencooled to 45°-50° C.

A solution of hydroxylamine sulphate (98.5 g) in water (300 g) was addedover 1 hour to the formylation reaction mixture at 45°-50° C. Stirringwas continued at that temperature for a further 1.5 hours after whichthe mixture was allowed to settle and the phases were separated.

An acid wash consisting of water (250 g) and sulphuric acid (16 g) wasadded to the organic phase and the mixture stirred at 45° C. for 0.5hour. The mixture was allowed to settle and the organic phase was washedwith water (2×125 g) at 50° C. Toluene was then removed from the organicphase by evaporation under reduced pressure to leave crude5-nonylsalicylaldoxime as a yellow oil (271 g). The oxime was purifiedby distillation at 180° C./0.55 mm Hg.

EXAMPLE 2

In a 500 ml three necked round bottom flask was placed 65.9 g5-nonylsalicylaldehyde at 90% strength in 48 ml toluene. To thissolution was added 2 ml of titanium tetraisopropoxide. The solutionbecame a reddish-brown colour immediately on addition of the titaniumcomplex. The contents were warmed to 45° C. and a solution of 21.8 g ofhydroxylamine sulphate in 35 ml water (pre-warmed to 40°-45° C.) wasadded over 30 seconds. The reaction mixture was stirred at 300 rpm and asolution of 14.5 g sodium carbonate in 30 ml water was added over 5minutes. The reaction temperature was maintained at 45° C. after theaddition was complete. The organic phase was sampled periodically andanalysed by GC for the presence of aldehyde. (6×1/8" column of 2%butanediol succinate on Chromosorb WHP). After two hours, analysisindicated 0.7% aldehyde remaining in solution. After three hours, thelevel of aldehyde had not changed significantly. The stirring wasstopped and the aqueous phase removed. The organic phase was washed with25 ml 5.6% sulphuric acid at 45° C. The aqueous phase was removed andthe organic phase washed twice with 35 ml water to a final pH of 2.6.The toluene was removed by rotary evaporation (2 mm Hg, bath temperature60° C.) to give 69.3 g red-brown oil. Analysis by Cu loading andtitration indicated oxime strength of 86.1%.

EXAMPLE 3

The procedure described in Example 1 was repeated except that thehydroxylamine sulphate was replaced by an equivalent amount ofhydroxylamine itself (as a 50% solution in water). Addition of thehydroxylamine solution to the formylation reaction mixture produced ayellow milky suspension which slowly turned white. After 1 hour at 45°C., GC analysis showed the oximation reaction to be complete.

After drowning into aqueous sulphuric acid, the toluene layer was verymilky but cleared after being stirred for 3 hours. The toluene layer wasseparated from the aqueous layer, washed with acid then with water andwas filtered. Toluene was removed from the organic phase by rotaryevaporation to give 5-nonylsalicylaldoxime (87.9% strength) in 87%yield.

EXAMPLE 4

Into a 250 ml round bottomed three necked flask, fitted with amechanical stirrer, thermometer, and reflux condenser, were chargedmagnesium raspings (2.95 g, 0.12 mole), dry methanol (75 ml, 1.85 mole)and dry toluene (25 ml). To this was added an 8% solution of magnesiummethoxide in methanol (3 ml, 0.002 mole) and the reaction mixture wasthen heated to reflux. After several minutes, hydrogen evolution wasnoted. The mixture was heated under reflux for 1 hour until all of themagnesium had dissolved, giving a cloudy white solution/suspension, withno further hydrogen evolution.

P-dodecylphenol (46.8 g, 0.179 mole) was added and the resulting yellowsolution heated under reflux for 1 hour before cooling to roomtemperature under a drying tube overnight. Toluene (120 ml) was chargedand the equipment was rearranged for distillation with fractionation.The mixture was heated to remove the methanol as an azeotrope withtoluene until an internal temperature of 102° C. was reached. During thedistillation (at approx. 97° C.), the viscosity of the solution visiblyincreased. The fractionation column was then removed and a slurry ofparaformaldehyde (18 g, 0.6 mole) in toluene (40 ml) was added at100°-105° C. in portions over 1 hour with concurrent distillation ofsolvent and low boiling by-products (59 ml). The reaction was held at100°-105° C. for 1 hour before cooling to 55° C. for the oximationreaction.

A solution of hydroxylammonium sulphate (19.7 g, 0.12 mole) in water (70ml) was prepared at 40°-50° C., then added to the reaction vessel over30 minutes with rapid agitation. The reaction was continued for 3 hoursat 55° C., then cooled to 30°-40° C.

The agitator was stopped and the contents transferred to a separationfunnel. The aqueous layer was removed and the green/black organic layerwas then transferred back to the reaction vessel. A dilute solution ofsulphuric acid (13 g, 0.13 mole) in water (100 ml) was charged to thevessel and agitated for 20 minutes at 50° C. A rapid colour change toyellow occurred in the first minute. After this acid treatment, thecontents were again transferred to the separation funnel and the acidicaqueous layer was removed. This was followed by two hot (≈50° C.) waterwashes (2×100 ml). The solvent was removed by rotary evaporation toyield 53.25 g of a pale yellow oil. Some of this oil was then distilledusing a Leybold apparatus under the following conditions:

wall temp.=230° C., vacuum=2.0 mmHg, addition rate=8.0 ml min⁻¹.

This yielded a very pale yellow oil which was found to be 95.3% strengthby ¹ H NMR using benzyl acetate as a standard, to give an error of ±2%.This was then used as a standard in order to analyse the crude productby G.C. The crude product was found to be 89.3% strength, giving a yieldof 87.3% ±2% of 5-dodecylsalicylaldoxime.

EXAMPLE 5

In a 1.0 L round bottomed three necked flask, fitted with a mechanicalstirrer, thermometer, and reflux condenser, were charged magnesiumraspings (5.55 g, 0.228 mole), dry methanol (150 ml, 3.7 mole) and drytoluene (50 ml). To this was added an 8% solution of magnesium methoxidein methanol (5 ml, 0.004 mole) and the reaction mixture was then heatedto reflux. After several minutes, hydrogen evolution was noted. Themixture was heated under reflux for 1 hour until all of the magnesiumhad dissolved, giving a cloudy white solution/suspension, with nofurther hydrogen evolution.

P-chlorophenol (48.7 g, 0.38 mole) was added and the resulting yellowsolution heated under reflux for 11/2 hours before cooling to roomtemperature under a drying tube overnight. Toluene (240 ml) was chargedand the equipment was rearranged for distillation with fractionation.The mixture was heated to remove the methanol as an azeotrope withtoluene until an internal temperature of 100° C. was reached. During thedistillation (at approx. 87° C.), precipitation occurred giving a paleslurry. The reaction was then cooled to 90°-95° C. and the fractionationcolumn removed before starting the addition of a slurry ofparaformaldehyde (34.1 g, 1.14 mole) in toluene (80 ml) in portions over1 hour at 90°-95° C. with concurrent distillation of solvent and lowboiling by-products (100 ml). The reaction was held at 90°-95° C. for 1hour before cooling to 55° C. and conversion of the equipment to refluxfor the oximation reaction. A yellow slurry had been formed.

A solution of hydroxylammonium sulphate (37.3 g, 0.227 mole) in water(120 ml) was prepared at 40°-50° C., then added to the reaction vesselover 30 minutes with rapid agitation. The reaction was continued for41/2 hours at 55° C., then cooled to 30°-40° C. A white precipitate hadformed in the aqueous layer which dissolved on addition of 0.5% v/vsolution of sulphuric acid (200 ml).

The agitator was stopped and the contents transferred to a separationfunnel. The aqueous layer was removed and the purple/black organic layerwas then transferred back to the reaction vessel. A dilute solution ofsulphuric acid (16.6 g, 0.166 mole) in water (250 ml) was charged to thevessel and agitated for 20 minutes at 50° C. A rapid colour change toyellow occurred in the first minute. After this acid treatment, thecontents were again transferred to the separation funnel and the acidicaqueous layer was removed. This was followed by two hot (≈50° C.) waterwashes (2×100 ml). The solvent was removed by rotary evaporation toyield 49.6 g of a yellow waxy solid which was found to be 42.8% strengthby ¹ H NMR using benzyl acetate as a standard, to give a yield of 32.6%of 5-chlorosalicylaldoxime.

EXAMPLE 6

In a 1.0 L round bottomed three necked flask, fitted with a mechanicalstirrer, thermometer, and reflux condenser, were charged magnesiumraspings (5.85 g, 0.24 mole), dry methanol (150 ml, 3.7 mole) and drytoluene (50 ml). To this was added an 8% solution of magnesium methoxidein methanol (5 ml, 0.004 mole) and the reaction mixture was then heatedto reflux. After several minutes, hydrogen evolution was noted. Themixture was heated under reflux for 1 hour until all of the magnesiumhad dissolved, giving a cloudy white solution/suspension, with nofurther hydrogen evolution.

P-methoxyphenol (49.6 g, 0.4 mole) was added and the resulting yellowsolution heated under reflux for 2 hours before charging toluene (240ml) and converting the equipment for distillation with fractionation.Methanol was removed as an azeotrope with toluene until an internaltemperature of 100° C. was reached. During the distillation (at approx.78° C.), precipitation occurred giving a pale slurry. The reaction wasthen cooled to 90°-95° C. and the fractionation column removed beforestarting the addition of a slurry of paraformaldehyde (36.0 g, 1.2 mole)in toluene (80 ml) in portions over 1 hour at 90°-95° C. with concurrentdistillation of solvent and low boiling by-products (68 ml). Thereaction was held at 90°-95° C. for 1 hour before cooling to 55° C. andconversion of the equipment to reflux for the oximation reaction. Anorange solution had been formed.

A solution of hydroxylammonium sulphate (39.4 g, 0.24 mole) in water(120 ml) was prepared at 40°-50° C., then added to the reaction vesselover 30 minutes with rapid agitation. The reaction was continued for41/2 hours at 55° C., then cooled to room temperature under nitrogenovernight. A white precipitate had formed in the aqueous layer whichdissolved on addition of 0.5% v/v solution of sulphuric acid (200 ml). Abrown precipitate had also formed in the organic layer. An attempt todissolve this was made by addition of toluene (100 ml) and heating to50° C. but the solid remained.

The agitator was stopped and the contents transferred to a separationfunnel. The aqueous layer was removed and the brown crystallineslurry/solution organic layer was then transferred back to the reactionvessel, the solids remaining in the separation funnel being washed intothe flask with toluene (80 ml). A dilute solution of sulphuric acid(16.6 g, 0.166 mole) in water (250 ml) was charged to the vessel andagitated for 20 minutes at 50° C. A rapid colour change to yellowoccurred in the first minute. After this acid treatment, the contentswere again transferred to the separation funnel and precipitationoccurred. The cloudy acidic aqueous layer was separated, and the organicsolution removed. Dichloromethane was added to dissolve the solids, andthen combined with the toluene solution above. The cloudy acidic aqueouslayer and the aqueous layer from the reaction mixture were bothextracted separately using dichloromethane (200 ml). All of the organiclayers were combined and the solvent was removed by rotary evaporationto yield 60.5 g of a yellow waxy solid. This solid was thenrecrystallised from toluene (250 ml) by heating to <70° C. followed bycooling in an ice bath to 0° C. and filtration of the precipitate. Thisgave 37.1 g of a pale off white solid which was found to be 90.4%strength by ¹ H NMR using benzyl acetate as a standard. The toluenefiltrates were rotary evaporated, giving 24.45 g of a brown oil, whichlater solidified. This was 26.7% strength by ¹ H NMR using benzylacetate as a standard to give a total yield of 60% of5-methoxysalicylaldoxime.

EXAMPLE 7

In a 1.0 L round bottomed three necked flask, fitted with a mechanicalstirrer, thermometer, and reflux condenser, were charged magnesiumraspings (5.85 g, 0.24 mole), dry methanol (150 ml, 3.7 mole) and drytoluene (50 ml). To this was added an 8% solution of magnesium methoxidein methanol (5 ml, 0.004 mole) and the reaction mixture was then heatedto reflux. After several minutes, hydrogen evolution was noted. Themixture was heated under reflux for 1 hour until all of the magnesiumhad dissolved, giving a cloudy white solution/suspension, with nofurther hydrogen evolution.

O-cresol (43.2 g, 0.4 mole) was added and the resulting yellow solutionheated under reflux for 2 hours before cooling to room temperature undera drying tube overnight. Toluene (240 ml) was added and the equipmentwas rearranged for distillation with fractionation. Methanol was removedas an azeotrope with toluene until an internal temperature of 97° C. wasreached. During the distillation (at approx. 80° C.), precipitationoccurred giving a brown slurry. The reaction was then cooled to 90°-95°C. and the fractionation column removed before starting the addition ofa slurry of paraformaldehyde (36.0 g, 1.2 mole) in toluene (80 ml) inportions over 1 hour at 90°-95° C. with concurrent distillation ofsolvent and low boiling by-products (89 ml). The reaction was held at90°-95° C. for 1 hour before cooling to 55° C. and conversion of theequipment to reflux for the oximation reaction. A yellow slurry had beenformed.

A solution of hydroxylammonium sulphate (39.4 g, 0.24 mole) in water(120 ml) was prepared at 40°-50° C., then added to the reaction vesselover 30 minutes with rapid agitation. The reaction was continued for11/2 hours at 55° C. A white precipitate had formed in the aqueous layerwhich dissolved on addition of 0.5% v/v solution of sulphuric acid (250ml). The agitator was stopped and the contents transferred to aseparation funnel.

The aqueous layer was removed and the green/black organic layer was thentransferred back to the reaction vessel. A dilute solution of sulphuricacid (33.12 g, 0.331 mole) in water (250 ml) was charged to the vesseland agitated for 20 minutes at 50° C. A rapid colour change to yellowoccurred in the first minute. After this acid treatment, the contentswere again transferred to the separation funnel and the acidic aqueouslayer was removed. This was followed by two hot (≈50° C.) water washes(2×100 ml). The solvent was removed by rotary evaporation to yield 61.1g of a yellow solid which was found to be 55.1% strength by ¹ H NMRusing benzyl acetate as a standard, to give a yield of 55.7% of3-methylsalicylaldoxime.

EXAMPLE 8

In a 1.0 L round bottomed three necked flask, fitted with a mechanicalstirrer, thermometer, and reflux condenser, were charged magnesiumraspings (5.85 g, 0.24 mole), dry methanol (150 ml, 3.7 mole) and drytoluene (50 ml). To this was added an 8% solution of magnesium methoxidein methanol (5 ml, 0.004 mole) and the reaction mixture was then heatedto reflux. After several minutes, hydrogen evolution was noted. Themixture was heated under reflux for 1 hour until all of the magnesiumhad dissolved, giving a cloudy white solution/suspension, with nofurther hydrogen evolution.

M-cresol (43.2 g, 0.4 mole) was added and the resulting yellow solutionheated under reflux for 2 hours before cooling to room temperature undera drying tube overnight. Toluene (240 ml) was added and the equipmentwas rearranged for distillation with fractionation. Methanol was removedas an azeotrope with toluene until an internal temperature of 97° C. wasreached. During the distillation (at approx. 87° C.), precipitationoccurred giving a cream coloured slurry. The reaction was then cooled to95° C. and the fractionation column removed before starting the additionof a slurry of paraformaldehyde (36.0 g, 1.2 mole) in toluene (80 ml) inportions over 1 hour at 95° C. with concurrent distillation of solventand low boiling by-products (79 ml). The reaction was held at 95° C. for1 hour before cooling to 55° C. and conversion of the equipment toreflux for the oximation reaction. A yellow slurry had been formed.

A solution of hydroxylammonium sulphate (39.4g, 0.24 mole) in water (120ml) was prepared at 40°-50° C., then added to the reaction vessel over30 minutes with rapid agitation. The reaction was continued for 4 hoursat 55° C. The agitator was stopped and the contents transferred to aseparation funnel.

The aqueous layer was removed and the green/black organic layer was thentransferred back to the reaction vessel. A dilute solution of sulphuricacid (33.12 g, 0.331 mole) in water (250 ml) was charged to the vesseland agitated for 20 minutes at 50° C. A rapid colour change to yellowoccurred in the first minute. After this acid treatment, the contentswere again transferred to the separation funnel and the acidic aqueouslayer was removed. This was followed by two hot (≈50° C.) water washes(2×250 ml). The solvent was removed by rotary evaporation to yield 60.1g of a yellow solid which was found to be 61.3% strength by ¹ H NMRusing benzyl acetate as a standard, to give a yield of 61.0%.

EXAMPLE 9

In a 1.0 L round bottomed three necked flask, fitted with a mechanicalstirrer, thermometer, and reflux condenser, were charged magnesiumraspings (5.85 g, 0.24 mole), dry methanol (150 ml, 3.7 mole) and drytoluene (50 ml). To this was added an 8% solution of magnesium methoxidein methanol (5 ml, 0.004 mole) and the reaction mixture was then heatedto reflux. After several minutes, hydrogen evolution was noted. Themixture was heated under reflux for 1 hour until all of the magnesiumhad dissolved, giving a cloudy white solution/suspension, with nofurther hydrogen evolution.

P-cresol (43.2 g, 0.4 mole) was added and the resulting yellow solutionheated under reflux for 2 hours before cooling to room temperature undera drying tube overnight. Toluene (240 ml) was added and the equipmentwas rearranged for distillation with fractionation. Methanol was removedas an azeotrope with toluene until an internal temperature of 98° C. wasreached. During the distillation (at approx. 87° C.), precipitationoccurred giving a cream coloured slurry. The reaction was then cooled to95° C. and the fractionation column removed before starting the additionof a slurry of paraformaldehyde (36.0 g, 1.2 mole) in toluene (80 ml) inportions over 1 hour at 95° C. with concurrent distillation of solventand low boiling by-products (79 ml). The reaction was held at 95° C. for1 hour before cooling to 55° C. and conversion of the equipment toreflux for the oximation reaction. A yellow slurry had been formed.(During the formylation reaction a physical loss of ≈5% occurred due tofrothing with a corresponding loss of yield).

A solution of hydroxylammonium sulphate (39.4 g, 0.24 mole) in water(120 ml) was prepared at 40°-50° C., then added to the reaction vesselover 30 minutes with rapid agitation. The reaction was continued for11/2 hours at 55° C. The agitator was stopped and the contentstransferred to a separation funnel.

The aqueous layer was removed and the green/black organic layer was thentransferred back to the reaction vessel. A dilute solution of sulphuricacid (33.12 g, 0.331 mole) in water (250 ml) was charged to the vesseland agitated for 20 minutes at 50° C. A rapid colour change to yellowoccurred in the first minute. After this acid treatment, the contentswere again transferred to the separation funnel and the acidic aqueouslayer was removed. This was followed by two hot (≈50° C.) water washes(2×125 ml). The solvent was removed by rotary evaporation to yield 57.65g of a yellow solid which was found to be 77.3% strength by ¹ H NMRusing benzyl acetate as a standard, to give a yield of 73.8% of5-methylsalicylaldoxime.

EXAMPLE 10

In a 1.0 L round bottomed three necked flask, fitted with a mechanicalstirrer, thermometer, and reflux condenser, were charged magnesiumraspings (5.85 g, 0.24 mole), dry methanol (150 ml, 3.7 mole) and drytoluene (50 ml). To this was added an 8% solution of magnesium methoxidein methanol (5 ml, 0.004 mole) and the reaction mixture was then heatedto reflux. After several minutes, hydrogen evolution was noted. Themixture was heated under reflux for 1 hour until all of the magnesiumhad dissolved, giving a cloudy white solution/suspension, with nofurther hydrogen evolution.

2,4-dimethylphenol (48.8 g, 0.4 mole) was added and the resulting yellowsolution heated under reflux for 2 hours before cooling to roomtemperature under a drying tube overnight. Toluene (240 ml) was addedand the equipment was rearranged for distillation with fractionation.Methanol was removed as an azeotrope with toluene until an internaltemperature of 95° C. was reached. During the distillation (at approx.92° C.), the viscosity of the solution increased. The reaction was thencooled to 93° C. and the fractionation column removed before startingthe addition of a slurry of paraformaldehyde (36.0 g, 1.2 mole) intoluene (80 ml) in portions over 1 hour at 95° C. with concurrentdistillation of solvent and low boiling by-products (67 ml). Thereaction was held at 95° C. for 11/2 hours before cooling to 55° C. andconversion of the equipment to reflux for the oximation reaction. Ayellow solution had been formed.

A solution of hydroxylammonium sulphate (39.4 g, 0.24 mole) in water(120 ml) was prepared at 40°14 50° C., then added to the reaction vesselover 30 minutes with rapid agitation. The reaction was continued for11/2 hours at 55° C., before cooling to room temperature overnight. Awhite precipitate had formed in the aqueous layer which dissolved onaddition of 0.5% v/v solution of sulphuric acid (200 ml). A pale brownprecipitate had also formed in the organic layer. The solid in theorganic phase re-dissolved on heating to 50° C.

The agitator was stopped and the contents transferred to a separationfunnel. The aqueous layer was removed quickly due to a precipitateforming in the organic layer. The brown crystalline slurry/solutionorganic layer was then transferred back to the reaction vessel and someof the solids remaining in the separation funnel were washed into theflask with toluene (50 ml). A dilute solution of sulphuric acid (33.12g, 0.331 mole) in water (250 ml) was charged to the vessel and agitatedfor 20 minutes at 50° C. A rapid colour change to yellow occurred in thefirst minute. After this acid treatment, the contents were againtransferred to the separation funnel and the acidic aqueous layer wasremoved. This was followed by two hot (≈65° C.) water washes (2×125 ml).The organic layer which had already started to precipitate, was thentransferred to a conical flask and placed in an ice bath to complete theprecipitation. The solid was then filtered off giving a yield of ≈29 g.The filtrates were then reduced in volume to about half by rotaryevaporation giving a second crop which was again filtered off to yield≈13 g. This procedure was repeated and a third crop was obtained, yield≈5 g. The solids were combined to give a white solid weighing 47.8 gwhich was found to be 36.9% strength by ¹ H NMR using benzyl acetate asa standard. The filtrates were then rotary evaporated to dryness givinga yellow solid weighing 18.8 g which was found to be 22.4% strength by ¹H NMR using benzyl acetate as a standard. This gave a total yield of32.8% of 3,5-dimethylsalicylaldoxime.

EXAMPLE 11

In a 500 ml round bottomed three necked flask, fitted with a mechanicalstirrer, thermometer, and reflux condenser, were charged magnesiumraspings (2.92 g, 0.12 mole), dry methanol (80 ml, 2.0 mole) and drytoluene (20 ml). To this was added an 8% solution of magnesium methoxidein methanol (2 ml, 0.0015 mole) and the reaction mixture was then heatedto reflux. After several minutes, hydrogen evolution was noted. Themixture was heated under reflux for 1 hour until all of the magnesiumhad dissolved, giving a cloudy white solution/suspension, with nofurther hydrogen evolution.

O-sec-butylphenol (30.0 g, 0.2 mole) was added and the resulting yellowsolution heated under reflux for 3 hours before cooling to roomtemperature under a drying tube overnight. Toluene (120 ml) was chargedand the equipment was rearranged for distillation with fractionation.The mixture was heated to remove the methanol as an azeotrope withtoluene until an internal temperature of 102° C. was reached. During thedistillation, the mixture remained a thin stirrable green solution. Thereaction was then cooled to 90°-95° C. and the fractionation columnremoved before starting the addition of a slurry of paraformaldehyde(18.0 g, 0.6 mole) in toluene (40 ml) in portions over 1 hour at 95°-98°C. with concurrent distillation of solvent and low boiling by-products(62 ml). The reaction was held at 99° C. for 40 minutes before coolingto 55° C. and conversion of the equipment to reflux for the oximationreaction. A yellow solution had been formed.

A solution of hydroxylammonium sulphate (19.7 g, 0.12 mole) in water (60ml) was prepared at 40°-50° C., then added to the reaction vessel over30 minutes with rapid agitation. The reaction was continued for 21/2hours at 55° C., then cooled to room temperature overnight. A whiteprecipitate had formed in the aqueous layer which dissolved on additionof 0.5% v/v solution of sulphuric acid (200 ml), and heating to 45° C.

The agitator was stopped and the contents transferred to a separationfunnel. The aqueous layer was removed and the purple/black organic layerwas then transferred back to the reaction vessel. A dilute solution ofsulphuric acid (16.6 g, 0.166 mole) in water (100 ml) was charged to thevessel and agitated for 30 minutes at 50° C. A rapid colour change toyellow occurred in the first minute. After this acid treatment, thecontents were again transferred to the separation funnel and the acidicaqueous layer was removed. This was followed by two hot (≈50° C.) waterwashes (2×100 ml). The solvent was removed by rotary evaporation toyield 38.6 g of an orange oil which was found to be 14.4% strength by ¹H NMR using benzyl acetate as a standard, to give a yield of 14.4% of3-sec-butylsalicylaldoxime.

EXAMPLE 12

In a 500 ml round bottomed three necked flask, fitted with a mechanicalstirrer, thermometer, and reflux condenser, were charged magnesiumraspings (1.46 g, 0.06 mole), dry methanol (50 ml, 1.23 mole) and drytoluene (10 ml). To this was added an 8% solution of magnesium methoxidein methanol (1 ml, 0.00074 mole) and the reaction mixture was thenheated to reflux. After several minutes, hydrogen evolution was noted.The mixture was heated under reflux for 1 hour until all of themagnesium had dissolved, giving a cloudy white solution/suspension, withno further hydrogen evolution.

M-tert-butylphenol (15.0 g, 0.1 mole) was added and the resulting yellowsolution heated under reflux for 11/2 hours before cooling to roomtemperature under a drying tube overnight. Toluene (70 ml) was chargedand the equipment was rearranged for distillation with fractionation.The mixture was heated to remove the methanol as an azeotrope withtoluene until an internal temperature of 97° C. was reached. During thedistillation (at approx. 93° C.), the viscosity of the solutionincreased. The reaction was then cooled to 95° C. and the fractionationcolumn removed before starting the addition of a slurry ofparaformaldehyde (9.0 g, 0.3 mole) in toluene (20 ml) in portions over50 minutes at 93°-95° C. with concurrent distillation of solvent and lowboiling byproducts (34 ml). The reaction was held at 95° C. for 40minutes before cooling to 55° C. and conversion of the equipment toreflux for the oximation reaction. A yellow slurry had been formed.

A solution of hydroxylammonium sulphate (9.85 g, 0.06 mole) in water (30ml) was prepared at 40°-50° C., then added to the reaction vessel over30 minutes with rapid agitation. The reaction was continued for 2 hoursat 55° C., then cooled to room temperature overnight. A small amount ofwhite precipitate had formed in the aqueous layer which dissolved onaddition of 0.5% v/v solution of sulphuric acid (100 ml), and heating to50° C.

The agitator was stopped and the contents transferred to a separationfunnel. The aqueous layer was removed and the purple/black organic layerwas then transferred back to the reaction vessel. A dilute solution ofsulphuric acid (11.04 g, 0.11 mole) in water (50 ml) was charged to thevessel and agitated for 20 minutes at 50° C. A rapid colour change toyellow occurred in the first minute. After this acid treatment, thecontents were again transferred to the separation funnel and the acidicaqueous layer was removed. This was followed by two hot (≈50° C.) waterwashes (2×75 ml). The solvent was removed by rotary evaporation to yield16.7 g of a pale yellow oil, which later solidified. This was found tobe 73.0% strength by ¹ H NMR using benzyl acetate as a standard, to givea yield of 63.2%. Only one regioisomer (4-tert-butylsaiicylaldoxime) wasdetected by G.C. analysis.

EXAMPLE 13

In a 1.0 L round bottomed three necked flask, fitted with a mechanicalstirrer, thermometer, and reflux condenser, were charged magnesiumraspings (5.85 g, 0.24 mole), dry methanol (150 ml, 3.7 mole) and drytoluene (50 ml). To this was added an 8% solution of magnesium methoxidein methanol (5 ml, 0.004 mole) and the reaction mixture was then heatedto reflux. After several minutes, hydrogen evolution was noted. Themixture was heated under reflux for 1 hour until all of the magnesiumhad dissolved, giving a cloudy white solution/suspension, with nofurther hydrogen evolution.

Phenol (37.6 g, 0.40 mole) was added and the resulting yellow solutionheated under reflux for 45 minutes before cooling to room temperatureunder a drying tube overnight. Toluene (240 ml) was charged and theequipment was rearranged for distillation with fractionation. Themixture was heated to remove the methanol as an azeotrope with tolueneuntil an internal temperature of 95° C. was reached. During thedistillation (at approx. 90° C.), precipitation occurred giving a paleslurry. The reaction was then cooled to 90°-95° C. and the fractionationcolumn removed before starting the addition of a slurry ofparaformaldehyde (36.0 g, 1.2 mole) in toluene (80 ml) in portions over1 hour at 95° C. with concurrent distillation of solvent and low boilingby-products (100 ml). The reaction was held at 90°-95° C. for 1 hourbefore cooling to 55° C. and conversion of the equipment to reflux forthe oximation reaction. A yellow slurry had been formed.

A solution of hydroxylammonium sulphate (37.3 g, 0.227 mole) in water(120 ml) was prepared at 40°-50° C., then added to the reaction vesselover 30 minutes with rapid agitation. The reaction was continued for 2hours at 55° C., then cooled to 30°-40° C. and the agitator stopped. Apoor separation resulted which improved on addition of 1.0% v/v solutionof sulphuric acid (100 ml).

The contents of the reaction vessel were then transferred to aseparation funnel. The aqueous layer was removed and the purple/blackorganic layer was then transferred back to the reaction vessel. A dilutesolution of sulphuric acid (36.8 g, 0,368 mole) in water (250 ml) wascharged to the vessel and agitated for 20 minutes at 50° C. A rapidcolour change to yellow occurred in the first minute. After this acidtreatment, the contents were again transferred to the separation funneland the acidic aqueous layer was removed. This was followed by two hot(≈50° C.) water washes (2×100 ml). The solvent was removed by rotaryevaporation to yield 51.3 g of a yellow oil which later partiallysolidified, and was found to be 63.0% strength by ¹ H NMR using benzylacetate as a standard, to give a yield of 59.0% of salicylaldoxime.

EXAMPLE 14

In a 1.0 L round bottomed three necked flask, fitted with a mechanicalstirrer, thermometer, and reflux condenser, were charged magnesiumraspings (5.85 g, 0.24 mole), dry methanol (150 ml, 3.7 mole) and drytoluene (50 ml). To this was added an 8% solution of magnesium methoxidein methanol (5 ml, 0.004 mole) and the reaction mixture was then heatedto reflux. After several minutes, hydrogen evolution was noted. Themixture was heated under reflux for 1 hour until all of the magnesiumhad dissolved, giving a cloudy white solution/suspension, with nofurther hydrogen evolution.

α-Naphthol (57.6 g, 0.4 mole) was added and the resulting yellowsolution heated under reflux for 1 hour before cooling to roomtemperature under a drying tube overnight. Toluene (240 ml) was chargedand the equipment was rearranged for distillation with fractionation.Methanol was removed as an azeotrope with toluene until an internaltemperature of 99° C. was reached. During the distillation, the mixtureremained a thin stirrable dark brown solution. The reaction was thencooled to 90°-95° C. and the fractionation column removed beforestarting the addition of a slurry of paraformaldehyde (36.0 g, 1.2 mole)in toluene (80 ml) in portions over 11/2 hours at 95°-99° C. withconcurrent distillation of solvent and low boiling by-products (95 ml).The reaction was held at 97° C. for 11/2 hours before cooling to 55° C.and conversion of the equipment to reflux for the oximation reaction. Abottle green slurry had been formed.

A solution of hydroxylammonium sulphate (39.4 g, 0.24 mole) in water(120 ml) was prepared at 40°-50° C., then added to the reaction vesselover 30 minutes with rapid agitation. The reaction was continued for51/2 hours at 55° C., then cooled to room temperature overnight. Thebottle green precipitate had remained unchanged, but was nowpredominantly in the aqueous phase. The solid was filtered off from thetwo phases and dried, to give the crude1-hydroxynaphthalene-2-carboxaldehyde oxime (magnesium salt) weighing82.9 g.

EXAMPLE 15

In a 1.0 L round bottomed three necked flask, fitted with a mechanicalstirrer, thermometer, and reflux condenser, were charged magnesiumraspings (5.85 g, 0.24 mole), dry methanol (150 ml, 3.7 mole) and drytoluene (50 ml). To this was added an 8% solution of magnesium methoxidein methanol (5 ml, 0.004 mole) and the reaction mixture was then heatedto reflux. After several minutes, hydrogen evolution was noted. Themixture was heated under reflux for 1 hour until all of the magnesiumhad dissolved, giving a cloudy white solution/suspension, with nofurther hydrogen evolution.

β-Naphthol (57.6 g, 0.4 mole) was added and the resulting mixturesolidified. Toluene (200 ml) was added giving a thick slurry to which anaddition of methanol (50 ml) was made. The slurry was heated underreflux for 1 hour before cooling to room temperature under a drying tubeovernight. Toluene (240 ml) was charged and the equipment was rearrangedfor distillation with fractionation. Methanol was removed as anazeotrope with toluene until an internal temperature of 99° C. wasreached. During the distillation, the thick slurry increased inviscosity until the surface of the mixture was not being agitated. Thereaction was then cooled to 93°-95° C. and the fractionation columnremoved before starting the addition of a slurry of paraformaldehyde(36.0 g, 1.2 mole) in toluene (80 ml) in portions over 11/2 hours at95°-99° C. with concurrent distillation of solvent and low boilingby-products (72 ml). The reaction was held at 99° C. for 2 hours, atwhich point a sample was taken and the reaction was shown to beincomplete. A further addition of paraformaldehyde (20 g, 0.66 mole) asa slurry in toluene (40 ml) was therefore carried out over 25 minutes.The reaction was stirred at 99° C. for a further 2 hours before removalof excess toluene (120 ml) by distillation, followed by cooling to 55°C. and conversion of the equipment to reflux for the oximation reaction.A mustard yellow coloured slurry had been formed.

A solution of hydroxylammonium sulphate (39.4 g, 0.24 mole) in water(120 ml) was prepared at 40°-50° C., then added to the reaction vesselover 30 minutes with rapid agitation. The reaction was continued for 3hours at 55° C., then cooled to room temperature overnight. The mixturehad turned green. A white precipitate had formed in the aqueous layerwhich dissolved on addition of 0.5% v/v solution of sulphuric acid (200ml), and heating to 50° C. The agitator was stopped and a poorseparation resulted which improved on addition of common salt (25 g).

The contents of the reaction vessel were then transferred to aseparation funnel. The aqueous layer was removed and the brown organiclayer was then transferred back to the reaction vessel. A dilutesolution of sulphuric acid (36.8 g, 0.368 mole) in water (250 ml) wascharged to the vessel and agitated for 20 minutes at 50° C. No colourchange occurred. The brown solution was then transferred back to theseparation funnel and the acidic aqueous layer was removed. This wasfollowed by two hot (≈50° C.) water washes (2×100 ml). The solvent wasremoved by rotary evaporation to yield 70.4 g of crude2-hydroxynaphthalene-l-carboxaldehyde oxime.

EXAMPLE 16

Into a 1 L round bottomed three necked flask, fitted with a mechanicalstirrer, thermometer, and reflux condenser, were charged magnesiumraspings (14.6 g, 0.6 mole), dry methanol (284 ml, 7.0 mole) and drytoluene (112 ml). To this was added an 8% solution of magnesiummethoxide in methanol (5 ml, 0.004 mole) and the reaction mixture wasthen heated to reflux. After several minutes, hydrogen evolution wasnoted. The reaction was heated under reflux for 11/2 hours until all ofthe magnesium had dissolved, giving a cloudy white solution/suspension,with no further hydrogen evolution.

P-nonylphenol (220.0 g, 1.0 mole) was added and the resulting yellowsolution heated under reflux for 1 hour before cooling to roomtemperature under a drying tube overnight. Toluene (240 ml) was chargedand the equipment was rearranged for distillation with fractionationunder vacuum. The mixture was heated to remove the methanol as anazeotrope with toluene at a pressure of 380 mmHg, until an internaltemperature of 75° C. was reached. During the distillation (at approx.71° C.), the viscosity of the solution visibly increased. A slurry ofparaformaldehyde (90 g, 3.0 mole) in toluene (150 ml) was then added at75°-77° C. in portions over 2 hours with concurrent distillation ofsolvent and low boiling by-products (210 ml). The internal reactiontemperature was maintained at 75°-77° C. by means of a gradual reductionin pressure to 270 mmHg throughout the addition. The reaction was heldat 75° C./270 mmHg for 1 hour before releasing the vacuum, rearrangingthe equipment for reflux and cooling to 55° C. for the oximationreaction.

A solution of hydroxylammonium sulphate (98.5 g, 0.6 mole) in water (300ml) was prepared at 40°-50° C., then added to the reaction vessel over30 minutes with rapid agitation. The reaction was continued for 3 hoursat 55° C., then cooled to 30°-40° C.

The agitator was stopped and the contents transferred to a separationfunnel. The aqueous layer was removed and the purple/black organic layerwas then transferred back to the reaction vessel. A dilute solution ofsulphuric acid (18.4 g, 0.184 mole) in water (250 ml) was charged to thevessel and agitated for 20 minutes at 50° C. A rapid colour change toyellow occurred in the first minute. After this acid treatment, thecontents were again transferred to the separation funnel and the acidicaqueous layer was removed. This was followed by two hot (≈50° C.) waterwashes (2×250 ml). The solvent was removed by rotary evaporation toyield 261.8 g of a pale yellow oil which was found to be 87.0% strengthby G.C., giving a yield of 86.6% of 5-nonylsalicylaldoxime.

EXAMPLE 17

In a 1.0 L round bottomed three necked flask, fitted with a mechanicalstirrer, thermometer, and reflux condenser, were charged magnesiumraspings (5.85 g, 0.24 mole), dry methanol (150 ml, 3.7 mole) and drytoluene (50 ml). To this was added an 8% solution of magnesium methoxidein methanol (5 ml, 0.004 mole) and the reaction mixture was then heatedto reflux. After several minutes, hydrogen evolution was noted. Themixture was heated under reflux for 1 hour until all of the magnesiumhad dissolved, giving a cloudy white solution/suspension, with nofurther hydrogen evolution.

P-methoxyphenol (48.6 g, 0.39 mole) was added and the resulting yellowsolution heated under reflux for 1 hour before cooling to roomtemperature under a drying tube overnight. Toluene (240 ml) was chargedand the equipment was rearranged for distillation with fractionationunder vacuum. The mixture was heated to remove the methanol as anazeotrope with toluene at a pressure of 380 mmHg, until an internaltemperature of 75° C. was reached. During the distillation (at approx.64° C.), a precipitation occurred giving a pale slurry. A slurry ofparaformaldehyde (36 g, 1.2 mole) in toluene (80 ml) was then added at75°-77° C. in portions over 11/2 hours with concurrent distillation ofsolvent and low boiling by-products (63 ml). The internal reactiontemperature was maintained at 75°-77° C. by means of a gradual reductionin pressure to 270 mmHg throughout the addition. The reaction was heldat 75° C./270 mmHg for 1 hour before releasing the vacuum, rearrangingthe equipment for reflux and cooling to 55° C. for the oximationreaction. A solution of hydroxylammonium sulphate (39.4 g, 0.24 mole) inwater (120 ml) was prepared at 40°-50° C., then added to the reactionvessel over 30 minutes with rapid agitation. The reaction was continuedfor 3 hours at 55° C., then cooled to room temperature under nitrogenovernight. A brown precipitate had formed in the aqueous layer.

The solid was filtered off from the two phases and the filtrates werethen transferred to a separation funnel. The aqueous layer was removed.The solid filter cake and the organic layer were then transferred backto the reaction vessel and a dilute solution of sulphuric acid (36.8 g,0.368 mole) in water (250 ml) was charged and then agitated for 20minutes at 50° C. A rapid colour change to yellow occurred in the firstminute. After this acid treatment, the contents were transferred to theseparation funnel. The cloudy acidic aqueous layer was separatedquickly, due to a precipitate forming, and the organicsolution/suspension was washed with two hot (≈65° C.) water washes(2×100 ml). The toluene solution/suspension was then transferred to aconical flask and placed in an ice bath to complete the precipitation.The pale yellow solid (27.9 g) was then filtered off and dried. Thecloudy acidic aqueous layer and the aqueous layer from the reactionmixture were both extracted separately using dichloromethane (200 ml).The organic layers were combined (dichloromethane from aqueous extractsand the toluene filtrates) and the solvent was removed by rotaryevaporation to yield 33.6g of a yellow solid. Both solids were analysedby G.C. using a standard of known strength to give a combined yield of41% of 5-methoxysalicylaldoxime.

EXAMPLE 18

In a 1.0 L round bottomed three necked flask, fitted with a mechanicalstirrer, thermometer, and reflux condenser, were charged magnesiumraspings (5.85 g, 0.24 mole), dry methanol (150 ml, 3.7 mole) and drytoluene (50 ml). To this was added an 8% solution of magnesium methoxidein methanol (5 ml, 0.004 mole) and the reaction mixture was then heatedto reflux. After several minutes, hydrogen evolution was noted. Themixture was heated under reflux for 1 hour until all of the magnesiumhad dissolved, giving a cloudy white solution/suspension, with nofurther hydrogen evolution.

2,4-Dimethylphenol (48.8 g, 0.4 mole) was added and the resulting yellowsolution heated under reflux for 11/2 hours before cooling to roomtemperature under a drying tube overnight. Toluene (240 ml) was addedand the equipment was rearranged for distillation with fractionationunder vacuum. The mixture was heated to remove the methanol as anazeotrope with toluene at a reduced pressure of 380 mmHg, until aninternal temperature of 75° C. was reached. During the distillation (atapprox. 71° C.), the viscosity of the solution visibly increased. Aslurry of paraformaldehyde (36.0 g, 1.2 mole) in toluene (80 ml) wasadded at 75°-77° C. in portions over 2 hours with concurrentdistillation of solvent and low boiling by-products (100 ml). Theinternal reaction temperature was maintained at 75°-77° C. by means of agradual reduction in pressure to 245 mmHg throughout the addition. Thereaction was held at 75° C./245 mmHg for 1 hour before releasing thevacuum, rearranging the equipment for reflux and cooling to 55° C. forthe oximation reaction. A yellow solution had been formed.

A solution of hydroxylammonium sulphate (39.4 g, 0.24 mole) in water(120 ml) was prepared at 40°-50° C., then added to the reaction vesselover 30 minutes with rapid agitation. The reaction was continued for 3hours at 55° C., before cooling to room temperature overnight. A whiteprecipitate had formed in the aqueous layer which dissolved on additionof 0.5% v/v solution of sulphuric acid (200 ml). A pale brownprecipitate had also formed in the organic layer. The solid in theorganic phase re-dissolved on heating to 50° C.

The agitator was stopped and the contents transferred to a separationfunnel. The aqueous layer was removed quickly due to a precipitateforming in the organic layer. The brown crystalline slurry/solutionorganic layer was then transferred back to the reaction vessel, some ofthe solids remaining in the separation funnel were washed into the flaskwith toluene (50 ml). A dilute solution of sulphuric acid (33.12 g,0.331 mole) in water (250 ml) was charged to the vessel and agitated for20 minutes at 50° C. A rapid colour change to yellow occurred in thefirst minute. After this acid treatment, the contents were againtransferred to the separation funnel and the acidic aqueous layer wasremoved. This was followed by two hot (≈65° C.) water washes (2×200 ml).The organic layer, which had already started to precipitate, was thentransferred to a conical flask and placed in an ice bath to complete theprecipitation. The solid was filtered off giving a yield of 41.5 g. Thefiltrates were then rotary evaporated to yield 26.9 g of a yellow solid.Both solids were analysed by G.C. using a standard of known strength togive a combined yield of 57.5% of 3,5-dimethylsalicylaldoxime.

I claim:
 1. A method for the preparation of a 2-hydroxyarylaldoximewhich comprises reacting hydroxylamine or a salt thereof with a2-hydroxyarylaldehyde, said reaction being performed in the presence ofa compound of magnesium, aluminum, titanium, zirconium or chromiumand/or under such conditions that the 2-hydroxyarylaldehyde is at leastpartially in the form of a salt and/or complex of magnesium, aluminum,titanium, zirconium or chromium.
 2. A method according to claim 1wherein the 2-hydroxyarylaldehyde has the formula: ##STR9## wherein eachof R¹, R², R³ and R⁴, independently, represents a hydrogen or halogenatom or an alkyl, cycloalkyl, aralkyl, aryl, alkaryl, alkoxy, aryloxy,acyl or hydroxy group.
 3. A method according to claim 2 wherein each ofthe alkyl, cycloalkyl, aralkyl, aryl, alkaryl, alkoxy, aryloxy or acylgroups which may be represented by R¹, R², R³ and R⁴ contains from 1 to36 carbon atoms.
 4. A method according to claim 2 wherein the2-hydroxyarylaldehyde has the formula: ##STR10## wherein R⁵ representshydrogen or a C₁₋₂₂ -alkyl radical.
 5. A method according to claim 4wherein R⁵ is a C₇₋₁₂ -alkyl radical.
 6. A method according to claim 2which comprises reacting hydroxylamine or a salt thereof with amagnesium bis-aryloxide derived from a 2-hydroxyarylaldehyde of Formula1 as defined in claim
 2. 7. A method according to claim 6 wherein themagnesium bis-aryloxide is derived from a 2-hydroxyarylaldehyde ofFormula 2: ##STR11## wherein R⁵ represents hydrogen or a C₁₋₂₂ -alkylradical.
 8. A method according to claim 7 wherein the magnesiumbis-aryloxide is magnesium bis-(2-formyl-4-nonylphenoxide).
 9. A methodaccording to claim 1 wherein the titanium compound is a titanium (IV)derivative.
 10. A method according to claim 1 wherein the2-hydroxyarylaldehyde used as reactant with the hydroxylamine is itselfthe direct product of reacting a phenol having at least one free orthoposition with formaldehyde or a formaldehyde-liberating compound undersubstantially anhydrous conditions in the presence of a compound ofmagnesium, aluminum, titanium, zirconium or chromium and the productthus formed is reacted with the hydroxylamine to form said2-hydroxyarylaldoxime.
 11. A method according to claim 10 whereinhydroxylamine or a hydroxylamine salt is reacted with a magnesium2-formylphenoxide obtained by reacting a magnesium bis-hydrocarbyloxidederived at least in part from a hydroxyaromatic compound having at leastone free position ortho to the hydroxyl group with formaldehyde or aformaldehyde liberating compound under substantially anhydrousconditions.
 12. A method according to claim 11 wherein the magnesium2-formylphenoxide is a magnesium bis(2-formylphenoxide) obtained byreacting a magnesium bis-phenoxide derived from a phenol having at leastone free ortho position with formaldehyde or a formaldehyde-liberatingcompound under substantially anhydrous conditions.
 13. A methodaccording to claim 12 wherein the magnesium 2-formylphenoxide is theproduct of reacting the magnesium bis-hydrocarbyloxide with formaldehydeor a formaldehyde-liberating compound in the presence of a substantiallyanhydrous solvent system comprising an inert non-polar or low polarityorganic solvent and a polar organic solvent.
 14. A method according toclaim 13 wherein the inert organic solvent comprises an aromatichydrocarbon or a chlorinated aromatic hydrocarbon.
 15. A methodaccording to claim 14 wherein the aromatic hydrocarbon comprises tolueneor xylene.
 16. A method according to claim 15 wherein the polar organicsolvent comprises a polar aprotic solvent or a lower alkanol.
 17. Amethod according to claim 16 wherein the lower alkanol comprisesmethanol.
 18. A method according to claim 11 wherein the magnesium2-formylphenoxide is the product of reacting the magnesiumbis-hydrocarbyloxide with formaldehyde or a formaldehyde-liberatingcompound at a pressure of from 50 to 700 mm Hg.
 19. A method accordingto claim 11 wherein the magnesium bis-hydrocarbyloxide is a magnesiumbis-phenoxide wherein the phenoxide residue may be unsubstituted or maybe substituted in any or all of the positions, other than both the 2-and 6- positions, by substituents which do not interfere with the courseof the reaction.
 20. A method according to claim t0 wherein themagnesium bis-phenoxide is derived-from a phenol of the formula:##STR12## wherein each of R¹, R², R³ and R⁴, independently, represents ahydrogen or halogen atom or an alkyl, cycloalkyl, aralkyl, aryl,alkaryl, alkoxy, aryloxy, acyl or hydroxy group.
 21. A method accordingto claim 20 wherein each of the alkyl, cycloalkyl, aralkyl, aryl,alkaryl, alkoxy, aryloxy or acyl groups which may be represented by R¹,R², R³ and R⁴ contains from 1 to 36 carbon atoms.
 22. A method accordingto claim 20 wherein the magnesium bis-phenoxide is derived from a phenolof the formula: ##STR13## wherein R⁵ represents hydrogen or a C₁₋₂₂-alkyl radical.
 23. A method according to claim 22 wherein R⁵ is a C₇₋₁₂-alkyl radical.
 24. A method according to claim 11 wherein the magnesiumbis-hydrocarbyloxide is the product of reacting a magnesium alkoxide ofthe formula:

    Mg(OR.sup.6).sub.2                                         ( 9)

wherein R⁶ represents an alkyl radical with up to two moles of a phenolhaving at least one unsubstituted position ortho to the hydroxyl group.25. A method according to claim 24 wherein the magnesiumbis-hydrocarbyloxide is the product of reacting the magnesium alkoxidewith from 0.9 to 2 moles of phenol per mole of magnesium alkoxide.
 26. Amethod according to claim 25 wherein the magnesium bis-hydrocarbyloxideis the product of reacting the magnesium alkoxide with from 1.5 to 2moles of phenol per mole of magnesium alkoxide.
 27. A method accordingto claim 24 wherein R⁶ is a C₁₋₄ -alkyl radical.
 28. A method accordingto claim 27 wherein the magnesium alkoxide is magnesium methoxide.
 29. Amethod according to claim 11 wherein the magnesium bis-hydrocarbyloxideis magnesium bis-(4-nonylphenoxide).